IGHV4-34

The IGHV4-34 gene encodes the immunoglobulin heavy variable region 4-34, a component of the B-cell receptor (BCR). This protein, also referred to as VH4-34, is notable for its intrinsic autoreactivity, particularly binding to self-antigens like the i/I carbohydrate epitopes on erythrocytes. It plays a critical role in B-cell development and antigen recognition, influencing BCR signaling pathways such as the PI3K/AKT, NF-κB, and MAPK cascades. Aberrant signaling through these pathways can lead to uncontrolled B-cell proliferation or survival. IGHV4-34-derived antibodies are frequently implicated in autoimmune disorders and B-cell malignancies due to their propensity to escape immune tolerance checkpoints.
IGHV4-34-utilizing BCRs are associated with systemic lupus erythematosus (SLE), cold agglutinin disease, and subsets of diffuse large B-cell lymphoma (DLBCL). Their pathogenic role stems from autoreactive antibody production or oncogenic mutations in downstream signaling mediators. Therapeutic strategies targeting these pathways include Bruton’s tyrosine kinase (BTK) inhibitors (e.g., ibrutinib) and anti-CD20 monoclonal antibodies (e.g., rituximab), which show efficacy in B-cell malignancies. Emerging approaches involve CAR-T therapies and bispecific antibodies, with clinical trials evaluating precision targeting of IGHV4-34-expressing clones in autoimmune and neoplastic contexts.

Popular Product:

Recombinant Human Ig heavy chain V-II region ARH-77